This proposal embraces possible connections between oncogenes and ion transport. It has long been known that tumor cells, unlike normal cells, can grow in calcium-deficient media. This difference may be explained by a new finding -- a calcium- and phorbol-inhibitable, bumetanide-resistant potassium-efflux pathway. In untransformed mouse NIH-3T3 cells, the efflux pathway opens when cells are in calcium-deficient media, and closes on addition of calcium or an active phorbol. In SV40-transformed NIH-3T3 cells, the efflux pathway is nearly closed in high or low calcium media. Studies are planned on possible modifiers of this efflux pathway, and will include changes in intracellular pH or cyclic AMP levels, and addition of channel blockers. A variety of oncogene- transformed NIH-3T3 cells will be tested to see if any show the same phenotypic properties of SV40-transformed NIH-3T3 cells: ability to grow in calcium-deficient media, and a nearly closed potassium-efflux pathway.